11-86408221-T-C

Position:

• chr11-86408221-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001156474.2(CCDC81):​c.1064T>C​(p.Ile355Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,716 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CCDC81 NM_001156474.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.66

Genes affected

CCDC81 (HGNC:26281): (coiled-coil domain containing 81) Located in centrosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2095668).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC81	NM_001156474.2	c.1064T>C	p.Ile355Thr	missense_variant	9/15	ENST00000445632.7	NP_001149946.1
CCDC81	NM_021827.5	c.794T>C	p.Ile265Thr	missense_variant	8/14		NP_068599.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC81	ENST00000445632.7	c.1064T>C	p.Ile355Thr	missense_variant	9/15	1	NM_001156474.2	ENSP00000415528	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461716 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727154

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 24, 2023

The c.1064T>C (p.I355T) alteration is located in exon 9 (coding exon 9) of the CCDC81 gene. This alteration results from a T to C substitution at nucleotide position 1064, causing the isoleucine (I) at amino acid position 355 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0075	.;T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.75	T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	.;M
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.11
Sift	Uncertain	0.0030	D;D
Sift4G	Uncertain	0.0060	D;D
Polyphen		0.40	B;P
Vest4		0.38
MutPred		0.18		.;Loss of stability (P = 0.0149);
MVP		0.37
MPC		0.36
ClinPred		0.91	D
GERP RS		4.3
Varity_R		0.13
gMVP		0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs969899330; hg19: chr11-86119263;